Depression Associated with Increased DNA Methylation

Epigenetics is an emerging field where researchers are studying the ways environmental events and biochemical changes can affect the structure of DNA. Chemicals such as methyl groups can accumulate on DNA (a process called methylation), which usually results in suppression of genes in that area. DNA is tightly wound around proteins called histones, which can also be methylated or acetylated (when acetyl groups accumulate) based on events in the environment, including stressors and drug use. The environmental events do not change the genetic inheritance people receive from their parents, but instead change the ease with which genes are transcribed (or switched on).

At the 2012 meeting of the Society of Biological Psychiatry, Dr. Yurong Xin et al. presented an abstract that indicates that depressed patients may have much more DNA methylation at CpG sites on genes. CpG sites occur in many genes and refer to a place where a cytosine and a guanine (two of the four building blocks of DNA) sit next to each other on the same strand of DNA (the ‘p’ refers to the chemical bond between the two). CpG sites can become methylated. Xin and colleagues measured 27,578 CpG sites across 14,000 genes in the human genome. They found an eightfold increase in DNA methylation at these CpG sites in depressed patients compared to controls.

Editor’s Note: Previous research has found that early life experiences like psychosocial stress can lead to epigenetic changes. The new findings by Dr. Xin indicate that DNA methylation may occur and accumulate across the lifespan and suggests that DNA methylation may be associated with the emergence and progression of depression. Future treatments for depression could target this DNA hypermethylation, but determining how to do that selectively without affecting normal functioning may be a challenge.

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